Identification of a structurally distinct CD101 molecule encoded in the 950-kb Idd10 region of NOD mice
Identification of a structurally distinct CD101 molecule encoded in the 950-kb Idd10 region of NOD mice
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DOI：
10.2337/diabetes.52.6.1551
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发表时间：
2003-06-01
期刊：
影响因子：
7.7
通讯作者：
Wicker, LS
中科院分区：
文献类型：
--
作者：
Penha-Gonçalves, C;Moule, C;Wicker, LS
影响自身免疫性1型糖尿病易感性的基因在非肥胖糖尿病（NOD）小鼠（Idd位点）已被映射使用同源株育种策略。在本研究中，我们使用的BAC克隆重叠群的建设，从同源株的DNA多态性分析，和人类orthopathy区域的序列挖掘的组合，以产生一个集成的地图，小鼠3号染色体上的Idd 10区域。在950-kb的Idd 10区域发现了7个基因和1个假基因。虽然所有7个基因的间隔是Idd 10候选人，我们建议的基因编码的EWI免疫球蛋白亚家族成员EWI-101（Cd 101）作为最有可能的Idd 10候选人，因为以前报道的免疫相关特性的人CD 101分子。另外的支持候选人的CD 101是存在17外显子的单核苷酸多态性，不同的NOD和B6序列，10个氨基酸取代的预测CD 101蛋白。这10个取代中有4个是非保守的，其中2个可能改变N-连接糖基化。考虑到我们的结果以及以前的那些报道，即识别人CD 101的抗体调节人T细胞和树突状细胞功能，现在有理由测试CD 101功能的改变是否影响自身免疫性胰岛破坏。糖尿病52：1551-1556，2003。
Genes affecting autoimmune type 1 diabetes susceptibility in the nonobese diabetic (NOD) mouse (Idd loci) have been mapped using a congenic strain breeding strategy. In the present study, we used a combination of BAC clone contig construction, polymorphism analysis of DNA from congenic strains, and sequence mining of the human orthologous region to generate an integrated map of the Idd10 region on mouse chromosome 3. We found seven genes and one pseudogene in the 950-kb Idd10 region. Although all seven genes in the interval are Idd10 candidates, we suggest the gene encoding the EWI immunoglobulin subfamily member EWI-101 (Cd101) as the most likely Idd10 candidate because of the previously reported immune-associated properties of the human CD101 molecule. Additional support for the candidacy of Cd101 is the presence of 17 exonic single-neucleotide polymorphisms that differ between the NOD and B6 sequences, 10 causing amino acid substitutions in the predicted CD101 protein. Four of these 10 substitutions are nonconservative, 2 of which could potentially alter N-linked glycosylation. Considering our results together with those previous reports that antibodies recognizing human CD101 modulate human T-cell and dendritic cell function, there is now justification to test whether the alteration of CD101 function affects autoimmune islet destruction. Diabetes 52:1551-1556, 2003.